A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines
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- 作者：Caterina M. Lombardo ; Sarah J. Welsh ; S ; ra J. Strauss ; Aaron G. Dale ; Alan K. Todd ; Rupesh Nanjunda ; W. David Wilson ; Stephen Neidle
- 关键词：HIF ; Renal cancer ; Sarcomas ; Small molecule ; Quadruplex
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：15 September, 2012
- 年：2012
- 卷：22
- 期：18
- 页码：5984-5988
- 全文大小：493 K
文摘
A series of naphthalene derivatives with disubstituted triazole side-arms have been assembled by click chemistry. Lead compounds show a high level of selectivity for renal, osteo- and Ewing¡¯s sarcomas that express the HIF-1¦Á transcription factor. They also interact selectively with the quadruplex DNAs located in the promoter of the HIF genes and it is suggested that the mechanism of action involves inhibition of transcription by drug-mediated quadruplex stabilization in these regions.